Endocrine Abstracts

Introduction: Metreleptin, a recombinant analogue of leptin, is the only drug available for the treatment of generalized or partial lipodystrophy. Familial partial lipodystrophy (FPL) is a rare genetic disorder characterized by selective loss of subcutaneous adipose tissue, ectopic fat deposition, decreased leptin levels, and varying metabolic disorders, which in some patients can be quite severe and life-threatening. We present here such a woman with FPL who is treated with metreleptin.

Presentation: A 53-year-old woman diagnosed with FPL (LMNA gene variant) 8 years ago, had the typical phenotypic features of the syndrome, type 2 diabetes mellitus (T2DM) (HbA1c=8.7%) and severe hypertriglyceridemia (triglycerides=1113.6 mg/dl) despite maximum treatment and good adherence to it. She also had extensive visceral fat, fatty liver with a marked increase in liver size, ectopic fat disposition with increased fat in the mediastinum and significant increase in pericardial fat, fibrosis of the heart septum and myocardiopathy. The patient commenced treatment with metreleptin 5.8mg per day subcutaneously. Three months after the initiation, she showed improvement in body weight and metabolic parameters (HbA1c=6.1% and triglycerides = 349 mg/dl). A year on metreleptin treatment, improvement of fatty liver infiltration and a significant reduction of its size (from 25cm to 20 cm) was observed as well as a significant reduction of the fat in the mediastinum and pericardium. Body composition measured by dual energy X-ray absorption (DXA), showed a fat redistribution with an increase in the upper and lower extremities and a decrease in the trunk. At two years on the same dose of metreleptin, she was metabolically stable (HbA1c=5.7% and triglycerides=320 mg/dl), with a further reduction of liver size, at 18 cm.

Conclusions: FPL is a rare disease with varying phenotype and a broad spectrum of metabolic disorders which at times can be quite severe and life-threatening. The use of metreleptin in these patients can significantly improve such metabolic aberrations and their potentially fatal consequences.